Indole and Benzimidazole Bichalcophenes: Synthesis, DNA Binding and Antiparasitic Activity.
Eur J Med Chem
; 143: 1590-1596, 2018 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-29126729
ABSTRACT
A novel series of indole and benzimidazole bichalcophene diamidine derivatives were prepared to study their antimicrobial activity against the tropical parasites causing African sleeping sickness and malaria. The dicyanoindoles needed to synthesize the target diamidines were obtained through Stille coupling reactions while the bis-cyanobenzimidazoles intermediates were made via condensation/cyclization reactions of different aldehydes with 4-cyano-1,2-diaminobenzene. Different amidine synthesis methodologies namely, lithium bis-trimethylsilylamide (LiN[Si(CH3)3]2) and Pinner methods were used to prepare the diamidines. Both types (indole and benzimidazole) derivatives of the new diamidines bind strongly with the DNA minor groove and generally show excellent in vitro antitrypanosomal activity. The diamidino-indole derivatives also showed excellent in vitro antimalarial activity while their benzimidazole counterparts were generally less active. Compound 7c was highly active in vivo and cured all mice infected with Trypanosoma brucei rhodesiense, a model that mimics the acute stage of African sleeping sickness, at a low dose of 4 × 5 mg/kg i.p. and hence 7c is more potent in vivo than pentamidine.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pentamidine
/
Trypanocidal Agents
/
Trypanosomiasis, African
/
Benzimidazoles
/
Trypanosoma brucei rhodesiense
/
Indoles
Limits:
Animals
Language:
En
Journal:
Eur J Med Chem
Year:
2018
Document type:
Article